Frustration Dynamics and Electron-Transfer Reorganization Energies in Wild-Type and Mutant Azurins

Long-range electron tunneling through metalloproteins is facilitated by evolutionary tuning of donor-acceptor electronic couplings, formal electrochemical potentials, and active-site reorganization energies. Although the minimal frustration of the folding landscape enables this tuning, residual frustration in the vicinity of the metallocofactor can allow conformational fluctuations required for protein function. We show here that the constrained copper site in wild-type azurin is governed by an intricate pattern of minimally frustrated local and distant interactions that together enable rapid electron flow to and from the protein. In contrast, sluggish electron transfer reactions (unfavorable reorganization energies) of active-site azurin variants are attributable to increased frustration near to as well as distant from the copper site, along with an exaggerated oxidation-state dependence of both minimally and highly frustrated interaction patterns.

Automated summary

This study investigates long-range electron tunneling through metalloproteins. The findings reveal that the rapid electron flow in wild-type azurin is facilitated by a pattern of minimally frustrated local and distant interactions, while sluggish electron transfer reactions in active-site azurin variants are attributed to increased frustration near and distant from the copper site.